8-109281080-A-T

Position:

• chr8-109281080-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032869.4(NUDCD1):​c.916T>A​(p.Phe306Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NUDCD1 NM_032869.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

Genes affected

NUDCD1 (HGNC:24306): (NudC domain containing 1) Predicted to be involved in immune system process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUDCD1	NM_032869.4	c.916T>A	p.Phe306Ile	missense_variant	6/10	ENST00000239690.9
NUDCD1	NM_001128211.2	c.829T>A	p.Phe277Ile	missense_variant	6/10
NUDCD1	XM_047422330.1	c.655T>A	p.Phe219Ile	missense_variant	6/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUDCD1	ENST00000239690.9	c.916T>A	p.Phe306Ile	missense_variant	6/10	1	NM_032869.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460806 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.916T>A (p.F306I) alteration is located in exon 6 (coding exon 6) of the NUDCD1 gene. This alteration results from a T to A substitution at nucleotide position 916, causing the phenylalanine (F) at amino acid position 306 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.00022	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.00096	T;.
Eigen	Benign	-0.088
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.050	N;N
REVEL	Benign	0.10
Sift	Benign	0.43	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.20	B;B
Vest4		0.71
MutPred		0.56		Gain of catalytic residue at P308 (P = 0.0571);.;
MVP		0.20
MPC		0.16
ClinPred		0.84	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-110293309;